Gene Expression Test Reduces Need for Invasive Heart Muscle Biopsy

Results of IMAGE Study Show Safe Reduction of Invasive Heart Biopsy

NewYork-Presbyterian/Columbia Physician-Scientist Is Author of Study in New England Journal of Medicine

NEW YORK(Apr 23, 2010)

Monitoring rejection in heart transplantation patients with a simple blood test co-developed by NewYork-Presbyterian Hospital/Columbia University Medical Center physician-scientist Dr. Mario Deng in 2005 can safely reduce their need for invasive heart-muscle biopsies, a new study has found.

The multicenter study called Invasive Monitoring Attenuation by Gene Expression (IMAGE) included research by Dr. Deng. Results were presented at the Annual Scientific Meeting of the International Society for Heart and Lung Transplantation in Chicago and are published online in the New England Journal of Medicine today.

Researchers looked at an FDA-cleared gene expression test called AlloMap molecular expression testing, which measures 11 genes from molecular pathways in white blood cells associated with heart transplant rejection. They found the approach was safe, resulted in significantly fewer biopsies compared with a traditional strategy of routine biopsies, and was preferred by patients.

"The genomics revolution initiated by the completion of the Human Genome Project has made possible what was only dreamed about before — namely the ability to improve patient care by ruling out rejection without taking an invasive heart tissue sample," says Dr. Mario Deng, director of cardiac transplantation research at Columbia University Medical Center, associate professor of medicine at Columbia University College of Physicians and Surgeons and a cardiologist at NewYork-Presbyterian Hospital/Columbia University Medical Center.

After the first year of transplant, heart transplant patients have an average risk of 3 to 5 percent for moderate or severe rejection. Rejection of a transplanted heart can lead to heart damage and eventual failure and loss of life. Consequently, for the rest of their lives, patients must be monitored for rejection to guide their immunosuppressant drug therapy.

Investigators randomly assigned 602 patients who were six months to five years since their heart transplantation to undergo rejection monitoring using either gene-expression profiling or routine endomyocardial biopsy, in addition to clinical and echocardiographic assessment of graft function. They compared the two groups for a composite primary outcome of rejection with heart function compromise, graft dysfunction due to other causes, death, or retransplantation. They found that during a median follow-up of 19 months, patients monitored with gene-expression profiling, as compared with those who underwent routine biopsies, had similar two-year cumulative rates of the composite primary outcome. The two-year rates of all-cause mortality were also similar in the gene-expression profiling and biopsy arms. Patients in the gene-expression profiling group underwent one-sixth the number of biopsies per person-year of follow-up compared with patients in the biopsy group. (For those in the gene expression test group, biopsies were performed when the test indicated an elevated risk for rejection, or if there were other clinical indications of rejection via cardiogram or symptoms.)

The new findings build on development and validation the Allomap® blood test published in a research study called CARGO (Cardiac Allograft Rejection Gene Expression Observational Study) in 2005 (Deng et al, American Journal of Transplantation). The CARGO-study, whose lead author was Dr. Deng, showed that the blood test could detect whether a chronic heart transplant patient is rejecting his heart, and reduce the need for invasive heart-muscle biopsies.

Beyond their instrumental role in the development of the original AlloMap molecular test and now its safe implementation into routine patient care, Dr. Deng's team has also spearheaded research into how this test works, specifically how the biological activity of white blood cell genes is linked to rejection in the transplanted heart. They found that the higher the rejection-related immunological activity in the white cell of the heart recipient, the slower the transplanted heart's electrical activity is spreading and the weaker the muscle is pumping. This research is in print in the Journal of Heart and Lung Transplantation and will be presented at the ISHLT meeting in Chicago by Dr. Deng's postdoctoral scientist Dr. Khurram Shahzad of Columbia University Medical Center.

Based on this groundbreaking translational research, NewYork-Presbyterian/Columbia is offering AlloMap blood test monitoring as an alternative to invasive biopsy to all heart transplant patients who are stable. The AlloMap test is the first transplantation test cleared by the U.S. Food and Drug Administration in the novel category of In Vitro Diagnostic Multivariate Index Assay (IVDMIA) category. More than 1,000 of these AlloMap blood tests have been done since inception of the program in 2006 at NYP/Columbia, and more than 20,000 tests in most U.S. heart transplantation centers.

"As the country's largest heart transplant program, our Hospital is taking the lead in offering our patients this cutting-edge tool to improve patients' quality of life," says Dr. Deng.

AlloMap molecular expression testing is a service provided by XDx through its clinical laboratory, which is Clinical Laboratory Improvement Amendments–certified to perform AlloMap testing for heart transplant patients nationwide.

Dr. Michael Pham and Dr. Hannah Valantine of Stanford University Medical Center are co-chairs of the IMAGE Study. Additional investigators include Dr. Jeffrey Teuteberg of the University of Pittsburgh Medical Center; Dr. Abdallah Kfoury of Intermountain Medical Center and Intermountain Healthcare; Dr. Randall Starling of the Cleveland Clinic; Dr. Thomas Cappola of the Hospital of the University of Pennsylvania; Dr. Andrew Kao of the Mid-America Heart Institute, St. Luke's Hospital; Dr. Allen Anderson of the University of Chicago Medical Center; Dr. William Cotts of Northwestern University; Dr. Gregory Ewald of Washington University School of Medicine; Dr. David Baran of Newark Beth Israel Medical Center; Dr. Roberta Bogaev of the Texas Heart Institute; and Barbara Elashaff, Dr. Helen Baron and Dr. James Yee of XDx.

XDx funded the study and XDx will be the sole proprietor of this technique. Though the collection of the sample is a simple blood draw, the analysis has the potential to, but may not necessarily, reduce the overall cost of transplant.

NewYork-Presbyterian Hospital

NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,353 beds. The Hospital has more than 1 million inpatient and outpatient visits in a year, including more than 220,000 visits to its emergency departments — more than any other area hospital. NewYork-Presbyterian provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian Hospital/Westchester Division. One of the most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and State and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation's largest not-for-profit, non-sectarian hospital provider. For more information, please visit www.cumc.columbia.edu.